PHLPP Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA. Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons. Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis. Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation. Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylates RAF1 inhibiting its kinase activity. May act as a negative regulator of K-Ras signaling in membrane rafts. Involved in the hippocampus-dependent long-term memory formation. Involved in circadian control by regulating the consolidation of circadian periodicity after resetting. Involved in development and function of regulatory T-cells. In colorectal cancer tissue, expression is highest in the surface epithelium of normal colonic mucosa adjacent to the cancer tissue but is largely excluded from the crypt bases. Expression is lost or significantly decreased in 78% of tested tumors (at protein level). Ubiquitously expressed in non-cancerous tissues. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC; Protein phosphatase, Ser/Thr (non-receptor); Tumor suppressor
Chromosomal Location of Human Ortholog: 18q21.33
Cellular Component:  cytosol
Molecular Function:  metal ion binding; protein binding
Biological Process:  apoptotic process; entrainment of circadian clock; negative regulation of protein kinase B signaling; regulation of apoptotic process; regulation of JNK cascade; regulation of MAPK cascade; regulation of p38MAPK cascade; regulation of T cell anergy
Reference #:  O60346 (UniProtKB)
Alt. Names/Synonyms: hSCOP; KIAA0606; MGC161555; PH domain and leucine rich repeat protein phosphatase 1; PH domain leucine-rich repeat-containing protein phosphatase 1; PH domain-containing family E member 1; PHLP1; PHLPP; PHLPP1; pleckstrin homology domain containing, family E (with leucine rich repeats) member 1; Pleckstrin homology domain-containing family E member 1; PLEKHE1; PPM3A; protein phosphatase, Mg2+/Mn2+ dependent 3A; SCN circadian oscillatory protein; SCOP; Suprachiasmatic nucleus circadian oscillatory protein
Gene Symbols: PHLPP1
Molecular weight: 184,672 Da
Basal Isoelectric point: 5.88  Predict pI for various phosphorylation states
CST Pathways:  PI3K/Akt Signaling
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  InnateDB